Occurrence of parabens and their metabolites in the paired urine and blood samples from Chinese university students: Implications on human exposure
Introduction
Parabens, as a type of antimicrobial preservatives, are widely used in personal care products, cosmetics, pharmaceuticals, and foodstuffs (Asimakopoulos et al., 2014; Guo and Kannan, 2013; Liao et al., 2013). These compounds reportedly act as xenoestrogens (a class of endocrine disruptors chemicals, EDCs), which were estrogenic in vitro and in uterotrophic assays in vivo (Boberg et al., 2010; Haman et al., 2015). In vivo studies shown that parabens may adversely effect reproduction, development, and homeostasis (Kolatorova et al., 2018). Methylparaben (MeP) and propylparaben (PrP) are the most widely used parabens and usually combined in products (Kolatorova et al., 2017). The other widely used parabens are ethylparaben (EtP) and butylparaben (BuP) (Pycke et al., 2015). Although, parabens have long been used and are generally regarded as safe, several human health concerns have been raised because of the potential endocrine disrupting properties of these chemicals (Prusakiewicz et al., 2007; Shekhar et al., 2017).
The widespread exposure of humans to parabens has been linked to ingestion, skin absorption and inhalation (Kolatorova et al., 2018). Once uptaken, parabens are easily metabolized by esterases in the liver, and the main metabolite is p-hydroxy benzoic acid (4-HB) (Boberg et al., 2010). However, information on the exposure to human paraben metabolites is limited (Wang et al., 2015; Wang and Kannan, 2013a). Among the metabolites, methyl protocatechuate (OH–MeP) and ethyl protocatechuate (OH–EtP) are specific to MeP and PrP exposures, respectively; by contrast, 4-HB and 3,4-dihydroxy benzoic acid (3,4-DHB) are the nonspecific metabolites, as they originate from multiple sources with parabens (Karthikraj et al., 2018). The physicochemical properties of parabens and their metabolites are presented in Table S1 (Supplementary Material).
Several studies have suggested that parabens do not accumulate and entail short half-lives of less than 24 h in the human body (Boberg et al., 2010; Janjua et al., 2008; Wang and Kannan, 2013a, 2013b), and parabens are conjugated and mainly eliminated via the urine and sometimes eliminated through feces and bile (Janjua et al., 2008). However, parabens can still be detected in blood or serum samples (Hines et al., 2015; Carrasco-Correa et al., 2015). Therefore, the levels of parabens in the urine and blood can be used as biomarkers for recent human monitoring (Calafat et al., 2010; Frederiksen et al., 2011; Ma et al., 2013; Wang et al., 2015; Ye et al., 2006). An international biomonitoring study has indicated that exposure to parabens is common among different populations, especially young adults, considering that parabens have been detected in the urinary and blood concentrations of majority of previously tested subjects (Adoamnei et al., 2018; Asimakopoulos et al., 2014; Bellavia et al., 2019; Casas et al., 2011; Shekhar et al., 2017; Vela-Soria et al., 2013).
More than 1900 higher education institutions have been established in China, and approximately 39 million individuals are undergraduate university students (Peng, 2011). With the country's state of economic development, the consumption of personal care products by Chinese consumers has been escalated sharply at an annual growth rate of 15.4% in the past five years (Liu et al., 2017). The proportion of consumption of personal care products by Chinese university students is continuously increasing, this group, especially female university students, has also become the main force of personal care products (Liu et al., 2017). However, a previous study reported that 48% of cosmetics and personal care products contain MeP and PrP, and 13% of these products include BuP (Masten, 2005). Human exposure to parabens was documented in infants (Asimakopoulos et al., 2016), children (Casas et al., 2011; Rocha et al., 2018), pregnant women (Aker et al., 2016; Bellavia et al., 2019; Song et al., 2020), young adults (Adoamnei et al., 2018), and the elderly (Asimakopoulos et al., 2014). However, data about the exposure of university students to parabens are limited (Zhang et al., 2018). Moreover, no study has reported on the levels of parabens and their metabolites by using paired urine and blood samples.
In this study, we determined the urinary and blood concentrations of four widely used varieties of parabens (i.e., MeP, EtP, PrP, and BuP) and their four metabolites (i.e., OH–MeP, OH–EtP, 3,4-DHB, and 4-HB), which were collected form 196 university students based in Guangzhou City in Guangdong Province. This study is expected to fill the gap in biological monitoring data about human exposure to parabens. Moreover, the influences of age and gender on the concentrations of parabens and their metabolites were examined. Then, we estimated the partition between blood and urine and the samples’ daily intake of parabens. To our knowledge, this study is the first to report the levels of parabens and their metabolites in paired urine and blood samples of Chinese university students.
Section snippets
Chemicals and reagents
Four native standards (i.e., MeP, EtP, PrP, and BuP) and four metabolites (i.e., 4-HB, 3,4-DHB, OH–MeP, and OH–EtP) were obtained from Sigma-Aldrich (St. Louis, MO). Formic acid, ammonium acetate, and β-glucuronidase were obtained from Sigma-Aldrich (St. Louis, MO). The isotope-labeled internal standards, namely, 13C12–MeP, 13C12–EtP, 13C12-PrP, 13C12-BuP, and 13C12-4-HB, were obtained from Cambridge Isotope Laboratories (Andover, MA, USA). HPLC-grade methanol and ethyl acetate were purchased
Results and discussion
To our knowledge, this study is the first to report the concentrations of parabens and their metabolites in paired urine and blood of Chinese university students. The distribution of concentrations of the total (free plus conjugated forms) parabens and their metabolites in paired urine and blood samples in Chinese university students is presented in Table 1.
Conclusions
The results of the present study suggest that Chinese university students have a high risk of exposure to parabens. MeP was the major parent paraben, and 4-HB was the major metabolite in the urine and blood. Positive correlations were observed between urinary levels and blood levels. Furthermore, the concentrations of parabens and their metabolites in blood were at least one order of magnitude lower than the concentrations in urine, suggesting that urinary concentrations are good predictors of
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This study was supported by the National Key Research and Development Program of China (No. 2017YFA0205200), the National Natural Science Foundation of China (No. 31770964, 81571785, and 81771957), the “111” Project (No. B16021). We gratefully acknowledge the donors who contributed the urine or blood samples for this study.
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These authors contributed equally to this work.